A Bullet Proof vascular graft to prevent dialysis access cannulation injury

项目摘要 终末期肾病（ESRD）仅在美国就影响了75万人。血液透析 (HD)是一种维持生命的疗法，用于需要抽血的肾衰竭患者， 在透析机里循环这个过程需要反复的针刺， 通过手术建立的血管分流这些分流通常是通过连接动脉和静脉来实现的 使用人工合成导管（动静脉移植物[AVG]）;这些移植物虽然广泛使用，但存在以下问题： 许多缺点。首先，它们不允许立即插管，因为它们需要4分钟的初始时间， 用于植入后的组织结合和愈合。因此，超过85%的ESRD患者通过以下途径开始HD： 隧道透析导管（TDC），同时其AVG愈合。由于TDC与高发病率相关， 死亡率，植入后立即插管的AVG的前景可能会降低 这些患者的发病率。其次，由于插管操作不小心或不当而导致的HD入路损伤， 导致移植物材料降解、假性动脉瘤形成、出血、凝块和感染。没有 目前可用的AVG可在植入后立即插管， 针进入，并防止入路插管损伤。为了减少这些并发症，InnAVasc Medical， Inc.已经开发出一种直接进入血液透析移植物，旨在确保常规，成功 插管，防止移植物损伤，因此，可以促进更安全的家庭HD;防弹血管移植物（BPG）。 该移植物由生物相容性材料制成，设计用于立即止血，自密封 并且抵抗无意的后部和侧壁针穿透。在二期工程和前期可行性研究中 在临床研究中，我们证实了BPG可以成功植入所有受试者，并且器械良好 容忍。此外，插管室按预期工作，允许立即进入并防止 针相关的伤害。然而，由于软移植物到腔室过渡处缺乏足够的应变消除， 区域，早期移植物血栓形成率高于临床可接受的水平。我们已经测试了修改后的 与原始BPG相比，台架上的移植物在管腔完整性的所有方面均优于原始BPG。 此外，来自南美小型可行性研究的临床数据证实了新的应变消除 预防早期血栓形成。因此，我们有信心，经修订的BPG将在以下方面按预期执行： 在下一个计划的临床研究中评估功能、血流和通畅性。在第二B阶段，我们将进一步推广 制定修订后的BPG，并通过进行关键的临床研究来实现我们的项目特定目标。 旨在评价其用于ESRD受试者HD入路的安全性和有效性。这将是一个前景， 在美国7家研究中心进行的多中心、单组、临床研究，计划入组60例受试者 ESRD。510（k）申请将在六个月内提交给美国食品和药物管理局， 患者随访作为主要分析。

PROJECT SUMMARY End Stage Renal Disease (ESRD) affects more 750,000 individuals in the United States alone. Hemodialysis (HD) is a life-sustaining therapy for patients suffering from renal failure that requires blood to be withdrawn and cycled through a dialysis machine. This process requires repeated needle punctures and the consequent needle access to a surgically created vascular shunt. These shunts are often created by connecting an artery to a vein with a prosthetic synthetic conduit (arteriovenous graft [AVG]); these grafts, though widely used, suffer from many disadvantages. First, they do not allow for immediate cannulation as they require an initial period of 4 weeks for tissue incorporation and healing post implant. Thus, more than 85% of ESRD patients initiate HD via tunneled dialysis catheter (TDC) while their AVG heals. Because TDCs are associated with high morbidity and mortality rates, the prospect of an AVG that can be cannulated immediately post implantation may reduce morbidity in these patients. Second, HD access injuries caused by careless or poor cannulation practices can result in graft material degradation, pseudoaneurysm formation, bleeding, clots, and infections. There is no currently available AVG that offers immediate cannulation after implantation, facilitates successful, error-proof needle entry, and protects from access cannulation injury. To reduce these complications, InnAVasc Medical, Inc. has developed an immediate access hemodialysis graft that is deigned to assure routine, successful cannulation, prevents graft injury, and thus, could promote safer home HD; the Bullet Proof vascular graft (BPG). This graft is constructed of biocompatible materials and is designed to be immediately hemostatic, self-sealing and resistant to inadvertent posterior and sidewall needle penetration. In the Phase II project and early feasibility clinical study, we confirmed the BPG could be successfully implanted in all subjects and that the device was well tolerated. Furthermore, the cannulation chamber worked as intended to allow for immediate access and prevent needle-related injuries. However, due to a lack of adequate strain relief at the soft graft to chamber transition zones, there was a higher rate of early graft thrombosis than clinically acceptable. We have tested the revised graft on the bench compared to the original BPG and it outperforms the original in all aspects of luminal integrity. Furthermore, clinical data from a small feasibility study in South America confirmed the new strain relief prevented early thrombosis. Therefore, we are confident that the revised BPG will perform as expected in terms of function, flow, and patency in the next planned clinical study. In this Phase IIB, we will further the commercial development of the revised BPG and achieve our specific goal of the project by conducting a pivotal clinical study to evaluate its safety and effectiveness for HD access in subjects with ESRD. This will be a prospective, multicenter, single arm, clinical study conducted at seven sites in the US with a planned enrollment of 60 subjects with ESRD. A 510(k) application will be submitted to the US Food and Drug Administration with six months of patient follow-up as the primary analysis.